Posttraumatic stress disorder (PTSD) may stem from the formation of aberrant and enduring aversive memories. Some PTSD patients have recreationally used Cannabis, probably aiming at relieving their symptomatology. However, it is still largely unknown whether and how Cannabis or its psychotomimetic compound Δ9-tetrahydrocannabinol (THC) attenuates the aversive/traumatic memory outcomes. Here, we seek to review and discuss the effects of THC on aversive memory extinction and anxiety in healthy humans and PTSD patients. Medline, PubMed, Cochrane Library, and Central Register for Controlled Trials databases were searched to identify peer-reviewed published studies and randomized controlled trials in humans published in English between 1974 and July 2020, including those using only THC and THC combined with cannabidiol (CBD). The effect size of the experimental intervention under investigation was calculated. At low doses, THC can enhance the extinction rate and reduce anxiety responses. Both effects involve the activation of cannabinoid type-1 receptors in discrete components of the corticolimbic circuitry, which could couterbalance the low “endocannabinoid tonus” reported in PTSD patients. The advantage of associating CBD with THC to attenuate anxiety while minimizing the potential psychotic or anxiogenic effect produced by high doses of THC has been reported. The effects of THC either alone or combined with CBD on aversive memory reconsolidation, however, are still unknown. Current evidence from healthy humans and PTSD patients supports the THC value to suppress anxiety and aversive memory expression without producing significant adverse effects if used in low doses or when associated with CBD. Future studies are guaranteed to address open questions related to their dose ratios, administration routes, pharmacokinetic interactions, sex-dependent differences, and prolonged efficacy.

中文翻译：

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∆9-四氢大麻酚对厌恶记忆和焦虑的影响：一项来自人体研究的综述。

创伤后应激障碍（PTSD）可能源于异常和持久厌恶记忆的形成。一些PTSD患者消遣地使用了大麻，可能旨在减轻其症状。然而，仍然很大程度上未知大麻或其拟精神病化合物Δ9-四氢大麻酚（THC）是否会以及如何减弱厌恶/创伤性记忆的结果。在这里，我们试图回顾和讨论THC对健康人和PTSD患者的厌恶性记忆消失和焦虑的影响。检索Medline，PubMed，Cochrane图书馆和对照试验中央注册数据库，以识别经同行评审的已发表研究和1974年至2020年7月之间以英语发表的人类随机对照试验，包括仅使用THC和THC联合大麻二酚（CBD）的受试者）。计算了所研究实验干预的效果大小。在低剂量下，四氢大麻酚可提高灭绝速度并减少焦虑反应。两种作用都涉及在大麻脂回路的离散成分中激活大麻素1型受体，这可能有助于平衡PTSD患者中报告的“内源性大麻素低调”。据报道，将CBD与THC结合可减轻焦虑，同时最大程度地减少高剂量THC产生的潜在精神病或焦虑症的优势。然而，THC单独或与CBD结合对厌恶性记忆再巩固的影响仍然未知。健康人和PTSD患者的最新证据支持THC值可抑制焦虑和厌恶记忆表达，如果以小剂量使用或与CBD联合使用时不会产生明显的不良影响。保证未来的研究将解决与剂量比，给药途径，药代动力学相互作用，性别依赖性差异和疗效延长相关的开放性问题。